To the clinician treating primary headache disorders, appreciation of pathophysiologic mechanisms is not less important than his recognition of diagnostic characteristics. Indeed, both aspects are prerequisites to successful management of chronic or recurrent headache patients. Thus, although the major thrust of this presentation concerns the mechanisms of vascular headaches, a clinical review of all primary headache disorders is included.

Well-delineated models and procedural descriptions are noticeably missing from the clinical biofeedback literature dealing with the training of physiological self-control. As a consequence, optimal protocols for the assessment and training of self-control of physiological functions have not eventuated. The present article reviews evidence suggesting that researchers have (a) confused self-control training, assessment, and measurement of tonic response levels, (b) neglected to determine the degree of acquired physiological self-control, and (c) failed to report the relationship between level of acquired physiological control and clinical outcome. The article also proposes an assessment and training paradigm that may be useful in reducing these methodological problems in future biofeedback research.

There are few well-controlled biofeedback temperature training studies in the literature that have used children as subjects. The purposes of this study were (1) to evaluate whether children can learn to increase hand temperature, controlling for methodological factors that have been overlooked in previous experiments, and (2) to determine whether adding thermal biofeedback to autogenic phrases results in improved ability to produce voluntary increases in hand temperature over the use of autogenic phrases alone. Twenty-six subjects (ages 9–11) were divided into two groups of 13 subjects each. All subjects participated in four 35 to 45-minute sessions consisting of a stabilization phase, a training phase, and a post-training phase on 4 consecutive days. One group was trained to increase finger temperature with autogenic phrases only, and the other was trained with autogenic phrases plus thermal feedback. None of the subjects in either group learned to increase hand temperature significantly within sessions. There was a consistent and reliable decreasing trend within each session; however, finger temperature did increase (.27° F) for the first 8 minutes of the training phase. There was a significant increase in hand temperature from day 1 to days 3 and 4, and there were significant increases in temperature during the stabilization phase alone. There were no differential effects of treatments. Methodological issues concerning stabilization, the potential confounding effect of boredom and fatigue, and different training methods for children are discussed.

Summary

A patient with migraine headaches of the “cluster” variant type is presented in whom vasospasm of the middle cerebral artery, the anterior cerebral artery and the internal carotid artery triggered a pain episode identical in character and severity to the headaches which had led to her investigation. Vasospasm associated with the painful phase of headache in this case conflicts with the more accepted theory that the pain phase of a vascular headache is related to vasodilatation of cerebral or extracerebral vessels. The literature is reviewed.

Summary

Synopsis: Since previously reviewed in the Journal (Vol. 12, No. 2), metoclopramide has been confirmed as an effective drug in treating and preventing various types of vomiting and as a useful agent in oesophageal reflux disease, gastroparesis, dyspepsia, and in a variety of functional gastrointestinal disorders. Of considerable importance is the recent evidence of its efficacy when administered intravenously in high dosages in preventing severe vomiting associated with cisplatin. Good results have been achieved in patients not previously treated with cisplatin, but further studies are needed to determine its level of efficacy in patients who have experienced severe vomiting during earlier courses of cytotoxic therapy. Side effects consisting of mild sedation, diarrhoea and reversible extrapyramidal reactions have occurred, but are tolerated by many patients.

Pharmacodynamic Studies: Pharmacodynamic studies in man have shown that oral and intravenous metoclopramide rapidly influences gastrointestinal tract motility. The effect of the drug in increasing lower oesophageal sphincter pressure is more marked in volunteers than patients with reflux oesophagitis or pregnant patients, and appears to be directly related to basal pressure, dose and route of administration. Gastric emptying studies employing radioisotope-labelled liquid and solid meals have demonstrated increased emptying in patients with delayed gastric emptying associated with diabetes, vagotomy and other gastric surgery. The effect of metoclopramide on gastric contractions is most pronounced in the antrum. Metoclopramide stimulates contraction of intestinal smooth muscle, resulting in a decreased transit time through the small intestine, but any effect on colonic activity remains to be clarified. Metoclopramide is effective in preventing apomorphine-induced vomiting in man, and in animals prevents vomiting induced by apomorphine, hydergine, reserpine, tetrodotoxin and copper sulphate, by raising the threshold for vomiting at the chemoreceptor trigger zone as well as by peripheral mechanisms. Other effects on the gastrointestinal tract are thought to result from inhibition of dopaminergic receptors, potentiation of cholinergic effects and/or a direct action on smooth muscle.

The neuroleptic-like central nervous system effects of metoclopramide probably result from blockade of cerebral dopamine receptors by the parent drug rather than by a metabolite.

Oral or intravenous metoclopramide stimulates prolactin release in all recipients.

Pharmacokinetics: Peak plasma metoclopramide concentrations occur within 1 hour of oral administration. On average, concentrations 1 hour after 20 and 40mg doses are about 40 and 80 ng/ml, respectively, but may show interindividual variation because of ‘first-pass’ hepatic metabolism. In crossover studies, relative bioavailability was lower after rectal administration of 40mg than after an oral dose of 26.7mg. The mean volume of distribution is about 2 to 3 L/kg. Metoclopramide readily enters breast milk where drug concentrations exceed those in plasma 2 hours after oral administration. 80% of an oral dose is excreted in the urine within 24 hours, either as unchanged drug (20%) or sulphate and glucuronide conjugates of metoclopramide. Elimination half-life has been reported as 2.6 to 5 hours in healthy subjects and around 14 hours in patients with moderate to severe renal impairment.

Therapeutic Trials: Controlled trials have shown oral metoclopramide 30 to 40mg daily to alleviate the symptoms of gastro-oesophageal reflux relative to placebo and in some studies to also increase lower oesophageal sphincter pressure. However, as with many other drugs used in oesophageal reflux disease, endoscopic healing of oesophagitis has still to be adequately demonstrated with metoclopramide.

Some patients with gastroparesis associated with diabetes mellitus or vagotomy have benefited from treatment with metoclopramide 40mg daily. However, there are no established criteria to predict which patients may benefit most and gastric emptying rates are not a reliable indication of response.

Metoclopramide has been successfully used to treat dyspepsia, being more effective than placebo, the anticholinergic drug pipenzolate and the antiemetic agent prochlorperazine. Similarly, metoclopramide appears to be useful in a variety of functional gastrointestinal disorders including irritable bowel syndrome, spastic constipation, and functional diarrhoea but studies in these conditions and in dyspepsia have generally been poorly designed. There is no firm evidence that the drug promotes the healing of peptic ulcer.

Results of studies in the prevention of postoperative vomiting have been variable, with metoclopramide proving effective and comparable with the peripheral dopamine antagonist domperidone when administered intravenously immediately prior to general anaesthesia. As with other drugs used in prevention of postoperative vomiting, response to metoclopramide has been influenced by the interval between administration and induction of anaesthesia, the anaesthetic drugs, postoperative use of narcotic analgesics and variation in surgical procedures.

Recent well conducted studies have shown high dose intravenous metoclopramide (1 to 2 mg/kg for 5 or 6 doses) to be effective in preventing the severe vomiting caused by cisplatin therapy (50 to 120 mg/m2). Best results to date have been achieved in patients not previously exposed to antineoplastic drugs, and in patients previously treated with cisplatin whose initial vomiting had been well controlled. In patients receiving cisplatin for the first time, high dose metoclopramide was superior to placebo, intramuscular prochlorperazine and oral tetrahydrocannabinol.

Metoclopramide has been used to control vomiting associated with narcotic analgesics, radiation therapy, pregnancy, gastroenteritis, gastric carcinoma, hepatic and biliary disorders, chronic renal failure, cardiac disease and alcoholism. The delayed absorption caused by poor gastric emptying associated with migraine attacks appears to be corrected by metoclopramide, resulting in earlier attainment of therapeutic plasma concentrations of concomitantly administered analgesics, but this has yet to be confirmed in appropriately designed controlled trials.

The drug has been widely used as an adjunct in radiological examination of the small bowel to facilitate the passage of barium, and is useful in facilitating intubation and in speeding the passage of biopsy capsules across the pylorus.

Side Effects: At usual therapeutic doses metoclopramide is well tolerated. Side effects are generally mild and transient and seldom necessitate withdrawal of the drug. They consist principally of drowsiness, restlessness, bowel disturbances, dizziness and faintness after oral or parenteral administration. At usual doses, extrapyramidal effects are infrequent in adults, but occur more often at the higher dosages used to prevent vomiting caused by antineoplastic drugs and in patients with renal failure. These reactions respond to reduction of dose, withdrawal of the drug, or treatment with intramuscular benztropine, diphenhy-dramine or diazepam. A dose-related increase in drowsiness is evident with high intravenous doses used to treat cisplatin-induced vomiting. Further experience is needed to determine the incidence of side effects with high and intermediate doses of intravenous metoclopramide, particularly in children and young adults.

Dosage: The usual oral intramuscular or intravenous dose in adults is 10mg 3 or 4 times daily before meals or before symptoms are likely to occur. Children under 14 years should receive 0.1 mg/kg per dose, the total daily dose not to exceed 0.5 mg/kg/day.

For diagnostic purposes, the adult dose is 20mg orally 20 minutes before examination or 10 to 20mg parenterally 5 minutes before examination.

For the prevention of cisplatin-induced vomiting in adults, metoclopramide should be iluted in 50ml of an intravenous solution and infused over a period of at least 15 minutes. At present it is recommended that administration should begin 30 minutes before cisplatin and be repeated 2-hourly for 2 doses and 3-hourly for 3 doses. The initial doses should be 2 mg/kg, and if vomiting is controlled, subsequent doses may be decreased to 1 mg/g. However, the optimum dosage recommendations, particularly in children and young adults, remain to be established.

A blood volume pulse (BVP) biofeedback system is described that integrates BVP amplitude to provide a signal appropriate for auditory feedback. In comparison to binary BVP feedback methods, this integrated system offers the advantages of continuous feedback and increased scoring ease. The validity of this system was established by correlating the integrated BVP output with trough-to-peak measurements of the raw BVP signal during unassisted relaxation and temporal BVP biofeedback with eight migraine headache patients. Within-subject correlations of the integrated and raw BVP outputs ranged from .82 to .98 (X=.95). Although the integrated method admits unwanted BVP changes in rate, correlation analyses showed this confound factor to be small. Increments in biofeedback training effects were observed during the treatment course. Substantive migraine relief was achieved by the end of treatment and therapeutic gains were maintained at 1-year follow-up. In conclusion, it appears that this method successfully presents continuous auditory feedback from an integrated BVP signal resulting in therapeutic benefits to migraineurs.

Clinical applications of biofeedback have proliferated and considerable lore surrounding the application of these techniques has evolved. Many assertions about the effectiveness of biofeedback training are based on findings of the least well-controlled studies, while many of the better controlled studies have failed to show that biofeedback directly mediates target symptoms or is superior to other treatments. Steiner and Dince (1981) suggest that the failure of these controlled studies is primarily attributable to methodological deficiencies. We believe that the question of whether or not there is a specific effect of biofeedback training is still frequently confused with the question of whether or not the treatment package as a whole has therapeutic value. Biofeedback is often therapeutic; however, evidence is often lacking that its effectiveness is due to biofeedback-trained changes in a target physiological process.

When dealing with a patient who has a chronic or a life-threatening illness, physical illness receives utmost care but psychosomatic aspect very little. Thus, we speak of the “coronary” needing intensive care and the “psychosomatic” needing psychotherapy which in fact is responding to one part of the problem. The patient who suffers from a disease is neither psyche nor soma alone and will be grateful to you if he will derive benefit from a comprehensive therapy. The origin, perpetuation and treatment of psychosomatic illnesses are multifaceted. Focusing on one aspect of the problem to the exclusion of others is definitely not beneficial. I address myself primarily to the usefulness of psychoactive drugs in some of the physical disorders not to imply its exclusive value but to expose its synergestic value with other forms of therapy. In addition, the opposite problem, rather more serious, psychosomatic disorders secondary to psychoactive drug therapy will also be elucidated to impart the feeling that art of using the medication in the total treatment regime and not mere application is important.

Prostaglandins (PGs) are normally found in small or trace amounts in body tissues and cerebrospinal fluid (CSF) in the absence of stimulation. A wide variety of stimuli activate the enzyme phospholipase A2 of cell membranes to release arachidonic acid [cis-5, 8, 11, 14-icosatetraenoic acid (AA)], which is the main precursor of PGs in man.56 This lipid contains 20 carbons and 4 double bonds (C20:4) and is rapidly converted to oxygenated products by two distinct pathways. One pathway involves the enzyme lipoxygenase, which forms a number of unstable compounds (hydroperoxyarachidonic acids) of which little is known, but that may play a role in leukotaxis along with the PGs.73 Lipoxygenase is apparently found only in platelets, lungs, and white cells. The other pathway involves the enzyme cyclooxygenase (prostaglandin synthetase), which produces from AA the endoperoxide PGs (PGG2 and PGH2).

A sample of 49 chronic headache patients (35 vascular and 14 tension) was separated according to capacity for absorption (as measured by Tellegen & Atkinson's 1974 scale) into groups high in absorption and groups low in absorption, with patients in the middle range being excluded. Absorption capacity was found to affect response to treatment in complex ways. Vascular headache patients high in absorption were significantly improved following relaxation training, but not after biofeedback training. Vascular headache patients low in absorption were significantly improved after biofeedback training. Tension headache patients low in absorption did not respond significantly to either form of treatment, while those high in absorption responded significantly to biofeedback training. Reasons for these differences in response to treatment were discussed.